Project Summary I, Dr. Ryan Kolb, am an assistant research scientist at the University of Iowa. I plan to pursue a career as an independent researcher with a tenure-track faculty position at an academic research institution, so that I may continue my research that I have developed during my training at the University of Iowa. My research focuses on how interactions between cells in the tumor microenvironment affect tumorigenesis and disease progression. This K22 application focuses on one aspect of this research; how obesity-associated inflammation drives breast cancer progression. This research seeks to addresses an unmet problem in the cancer field. While, the link between obesity and breast cancer progression and a worse clinical outcome are well established, there has been no specific therapies developed to treat obese patients and obese patients are often excluded from clinical trials due to obesity-related complications. In Aim 1 of this proposal we will define the role of ANGPTL4 in obesity-driven breast cancer progression and provide a rationale for ANGPTL4 targeted therapies to treat obese breast cancer patients. Aim 2 will test the efficacy of targeting ANGPTL4 in preclinical models of obesity-driven breast cancer progression and characterize novel anti-human ANGPTL4 antibodies for their ability to inhibit ANGPTL4. Together these aims will promote the development of ANGPTL4 antibodies as a therapy to improve the outcome for obese breast cancer patients. The K22 award will be beneficial in my goal to transition into an independent cancer researcher. This award will allow me to pursue further training in clinical cancer research. As a basic scientist looking to transition into an independent career with a larger focus on translational cancer research, this training will be highly beneficial. My plan to successfully transition to an independent position and establish an independent research program involves applying for an R01 by the end of the first year of this award. The proposed aims in this K22 application will provide me with a solid foundation upon which to build a R01 application. Combined with my background in cancer biology and cancer immunology, this K22 award will greatly aid me in establishing a successful and impactful career as a translational cancer researcher in the tumor microenvironment field.